Method. A retrospective chart review. Patient demographics and
types of fetal anomalies were analysed according to the groups that
accepted or declined late termination of pregnancy (LTOP, >24 weeks)
for severe congenital abnormalities.

Results. Of 3 896 women referred to the Fetal Medicine Unit at
Inkosi Albert Luthuli Central Hospital, KwaZulu-Natal, 2 209 (56.7%)
were at >24 weeks' gestation at their first visit. LTOP for
severe congenital abnormalities was offered to 253 (11.5%), of whom 191
(75.5%) accepted. Differences in maternal age, parity, race and religion
were not statistically significant. The type of fetal abnormalities and
gestational age at diagnosis influenced the decision-making process in
>80% of the women. The most frequent indications for LTOP were brain
and spinal abnormalities (53.0%), and aneuploidy (20.6%). Feticide by
ultrasound-guided intracardiac KCl injection was performed in 138/191
cases (72.2%); 53 women who accepted LTOP did not undergo feticide for a
variety of reasons. The mean interval between diagnosis and performance
of feticide was 10 days (range 0-42 days). Fetal asystole was achieved
in all cases within 2 minutes by a single-needle injection of
intracardiac KCl; the mean duration of the procedure was 12 minutes
(range 6 - 25 minutes). There were no maternal complications, and
stillbirths occurred in all cases.

Conclusion. Feticide by ultrasound-guided intracardiac KCl
injection was an acceptable, safe and effective method for LTOP. Further
studies are needed to determine the minimum dosage of KCl required to
achieve the desired effect.

The South African Choice on Termination of Pregnancy Act, No. 92 of
1996, allows termination of pregnancy (TOP) for severe fetal
abnormalities at any gestational age (GA). (1) Despite the provision of
free antenatal care to all pregnant women, the majority of those
attending public health institutions 'book' for antenatal care
in the late second or third trimester of pregnancy and miss the
opportunity for early prenatal diagnosis of major lethal congenital
abnormalities and early intervention if required. Limited resources and
expertise at public health institutions compound the problem of
diagnosing fetal abnormalities in early pregnancy. Consequently, many
abnormalities are detected only after the fetus is viable, i.e. at
[greater than or equal to] 24 weeks' gestation.

Congenital abnormalities likely to result in the birth of a
severely mentally or physically handicapped child necessitate discussing
outcomes and possible grounds for TOP. Decisions regarding late
termination of pregnancy (LTOP) should not involve just pregnant women,
their families and their clinician. Ideally there should be a consensus
agreement by a multidisciplinary team that governs the decision-making
process for approval of an LTOP. The multidisciplinary team must
carefully consider the legal and ethical implications of the clinical
decision that an anomaly is sufficiently severe for LTOP, (2) which
should take into account social, cultural, religious and psychological
viewpoints. Women should also be counselled about the clinical
management of pregnancies complicated by severe fetal anomalies. When
there is certainty about the diagnosis and the high probability of
either death or survival with severe and irreversible handicap as a
result of the anomaly diagnosed, the pregnant woman should be offered
the alternatives of aggressive versus non-aggressive obstetric
management. (3) It is also ethically permissible to offer feticide
followed by TOP after viability in such cases. Ideally, all women should
be informed about the need for autopsy and other appropriate
investigations following feticide or perinatal death for a severe fetal
anomaly, which allows accurate counselling regarding future pregnancies.
(4)

Deciding to terminate a viable pregnancy (where there is a chance
of ex utero survival) places the women, her family and health
professionals (including midwives) in a difficult situation. The chance
of a live birth following a medical termination increases with advancing
gestation. Crucial neonatal management decisions must be made if these
fetuses are born alive. Neonatologists are duty-bound to provide basic
palliative care for as long as the infant survives.

Irrespective of the reasons for late termination,5 feticide is
therefore performed to ensure that a viable fetus is stillborn. Several
methods of feticide have been described,6-11 including intracardiac or
intraumbilical potassium chloride or lignocaine injection to induce
cardiac asystole. For women who choose to terminate pregnancy with an
abnormal fetus at an advanced gestation, the method used must be safe
and effective. We report on our experiences of feticide with
intracardiac potassium chloride (KCl) injection for LTOP among women who
chose this option and the indications for and acceptance of LTOP in this
group.

Methods

Charts of women offered LTOP for severe congenital abnormalities
during August 2003-December 2008 at the Fetal Medicine Unit, Inkosi
Albert Luthuli Central Hospital (IALCH), KwaZulu Natal (KZN), were
retrospectively reviewed. IALCH is a tertiary/ quaternary referral
hospital and the only public health institution that performs LTOP by
feticide in this province. Institutional ethical and hospital permission
to perform this audit was obtained. The diagnosis of a severe fetal
malformation was based on level III ultrasound findings, with or without
adjunctive tests such as fetal magnetic resonance imaging and
karyotyping. Obstetric ultrasound examinations were performed using the
Siemens Acuson S2000 machine, with conventional 2D scan, colour and
spectral pulsed-wave Doppler. A fetal medicine specialist (LG) performed
all ultrasound scans with assistance from two experienced sonographers.

A severe fetal abnormality was diagnosed by consensus opinion of a
multidisciplinary team including fetal medicine specialist,
obstetrician, midwife, geneticist/paediatrician, bioethicist,
psychologist, social worker, genetic counsellor, and other experts
depending on the nature of the case, e.g. cardiologist, paediatric
surgeon or neurosurgeon. Counselling before TOP was provided to all the
women by two or more trained healthcare workers on two or more
occasions. Written informed consent was obtained from those who agreed
to LTOP by feticide.

The inclusion criteria included singletons and dichorionic twins
with severe fetal abnormalities at >24 weeks' gestation. The
patient demographics and types of fetal anomalies were analysed
according to the groups that accepted or declined LTOP. Reasons for
declining LTOP were documented. In the LTOP feticide group, the
following parameters were evaluated: GA when the procedure was
performed, duration of the procedure, amount of KCl used to achieve
permanent asystole, number of needle insertions to reach target,
procedure-related complications, procedure-to-delivery interval,
induction versus spontaneous labour, and any labour complications.
Information was captured using a clinical software package.

Procedure of feticide

The procedure was done on an outpatient basis by a fetal medicine
specialist. Other members of the team included a doctor (specialist
obstetrician or registrar in training) to aspirate heart blood,
administer the KCl and assist with concomitant procedures if indicated,
e.g. amniodrainage, cephalocentesis; a midwife to attend to the patient
and keep her comfortable during the procedure; a scrub sister to assist
with the procedure, including collecting and labelling blood specimens;
and a sonographer/assistant to 'drive' the ultrasound machine
as required during the procedure.

Owing to rotation of clinical staff and to minimise any chance of
errors, the assistant staff were regularly orientated on the invasive
procedure and their roles were explained before commencing. The wishes
of healthcare workers with personal objections to the performance of
feticide were respected. The requirements for the procedure, including
needles, heparinised syringes and drugs, were set up by the scrub
nursing sister, who is a dedicated staff member of the unit. The expiry
date and labelling of all drugs used for the procedure were
counter-checked by the fetal medicine specialist before commencing the
procedure. A fully equipped resuscitation trolley, which was checked
regularly, was available at the clinic. The mother's Rh status was
checked before the procedure, and if she was Rh negative the fetal heart
blood Rh was checked and the patient managed accordingly.

At least half an hour before the feticide procedure, all the
patients were given pethidine 50 mg intravenously for sedation and an
antiemetic if necessary. After excluding allergies, a second-generation
cephalosporin (mefoxin) 2 g was given intravenously as a prophylactic
antibiotic. The fetus was scanned to obtain a four-chamber view of the
fetal heart, and the fetal heart rate and procedure commencement time
were recorded. The procedure was performed in the scan room under
sterile conditions, using the free-hand technique and under continuous
ultrasound guidance. Lignocaine 2% was used to infiltrate the maternal
abdominal skin at the site of entry into fetal heart. A 20-gauge 15 cm
spinal needle was traversed through the predetermined tract, targeting
the left ventricle or alternatively the most accessible chamber of the
fetal heart. On confirming placement of the needle in the fetal heart by
direct sonographic visualisation of the needle tip, the assistant
removed the stylet. To reduce the risk of feto-maternal contamination
through the needle tract during insertion, the initial 1 ml of aspirated
heart blood was discarded. A specimen of heart blood was withdrawn for a
full blood count, a Kleihauer test, karyotyping and other investigations
as indicated, e.g. viral screen (TORCH and parvovirus) and other genetic
studies. Thereafter, the assistant doctor injected 2 ml of 15% KCl into
the fetal heart under direct vision. A further 2 ml was injected every
30 seconds until permanent fetal asystole was achieved, and the time was
recorded. The fetal heart was observed on scan for a further 5 minutes
of asystole with the needle in situ. To minimise any risk of maternal
contamination with KCl, the needle was flushed with 5 ml sterile water
or saline before removal.

All patients were observed and their vital signs assessed in the
clinic for 1 hour after the procedure. To confirm permanent fetal
asystole, a rescan was performed at least 30 minutes after the procedure
or just before the patient left the clinic. All 'low-risk'
women were referred back to their base hospital for standard obstetric
management and delivery including assessment by a social worker and a
psychologist, as indicated. Provided there were no contraindications to
vaginal delivery, the women were given the choice to have labour induced
or to await spontaneous onset of labour. The obstetric management was
the same as that of a woman presenting with a spontaneous intra-uterine
death after 24 weeks' gestation. This included weekly monitoring of
maternal blood coagulation profiles in those managed expectantly to
ensure that they did not develop a coagulopathy. Labour was induced if
women did not go into spontaneous labour within 3 weeks.

All women were given a 6-week follow-up appointment with the
genetic counsellor for on-going counselling and review of the fetal
blood results, and to record the perinatal outcome of those who declined
LTOP by feticide.

Statistical analysis

The numerical analysis was performed using the Statistical Package
for Social Sciences (SPSS) for Windows version 16.0 (SPSS Inc., Chicago,
Ill., USA) to explain the concepts that underpin the analyses. The data
were analysed as tables and figures. The groups that accepted and
declined TOP were compared with reference to their demographics, types
of fetal anomalies and delivery outcome. Frequency tables and
cross-tabulations reporting counts and percentages were used to describe
the distribution of the data. Pearson's chi-square test was used to
compare demographics and diagnoses between groups. Analysis of variance
testing with Bonferroni post-hoc tests was used to compare mean dose of
KCl between the GA categories. A p-value of <0.05 was considered to
be statistically significant.

[FIGURE 1 OMITTED]

Results

During the 5-year study period, 3 896 women were referred to the
Fetal Unit, of whom 2 209 (56.7%) were at [greater than or equal to] 24
weeks' gestation at first presentation. LTOP for severe congenital
abnormalities was offered to 253 women (study group), of whom 191
(75.5%) accepted (Fig. 1). The differences in the mean maternal age (26
years), parity (1) and GA at diagnosis (31+ weeks) between the accepted
and declined groups were not significant.

The most frequent indications for LTOP were brain and spinal
abnormalities (53.0%), aneuploidy (20.6%) and multiple congenital
abnormalities (11.5%). Table 1 compares the types and prevalences of
fetal abnormalities and the rates of acceptance of LTOP between the
groups. Although not statistically significant (p=0.06), the differences
between the groups that accepted or declined LTOP based on the type of
fetal anomaly were clinically important.

Of the 134 brain anomalies, 52 were hydrocephalus; 38 of these
women accepted LTOP, and half had concomitant cephalocentesis. There
were 27 cases of spina bifida, and in this group 16 women accepted LTOP.
Fig. 2 shows the distribution of the types of aneuploidy. Of women with
a confirmed diagnosis of fetal aneuploidy, 67.3% (35/52) accepted LTOP.
The commonest aneuploidy was trisomy 18 (28/52), and of these women 20
accepted LTOP. There were 9 cases each of trisomy 21 and trisomy 13.

Outcomes of fetal congenital abnormalities

Feticide by intracardiac KCl injection was performed in 138/191
cases in the accepted group (72.2%) at a mean GA of 33 weeks (range
26-41 weeks). The mean interval between diagnosis and feticide was 10
days (range 0-42); 53 women accepted but did not have LTOP feticide. Of
the 53, 22 had TOP between 24 and 26 weeks' gestation for a lethal
anomaly detected at borderline viability, which all resulted in a
stillbirth or death within 12 hours of birth. Twelve women booked for
feticide presented with intra-uterine fetal death before the
feticide-these cases included fetal anomalies complicated by fetal
hydrops, severe growth restriction, and fetuses with multiple anomalies.
The remaining 19 women who accepted LTOP did not return for the
procedure, were lost to follow-up, or delivered before their procedure
appointment.

The number of feticides performed per anomaly category was as
follows: central nervous system 65 (excluding neural tube defects),
neural tube defects 22, aneuploidy 18, multiple fetal abnormalities 17,
twin anomalies 5, skeletal 6, cardiac 3, and renal 2. Fetal asystole was
achieved in all cases within 2 minutes of intracardiac KCl injection
with mean volumes of 8 ml (GA 24-25 weeks), 10 ml (26-30 weeks) and 13
ml (>30 weeks) (p=0.001) (Table 2). The average duration of the
procedure was 12 minutes (range 6-25 minutes). Only one-third of the
women presented for the 6-week follow-up visit. Feticide-delivery
intervals, modes of delivery, and perinatal outcomes for those who opted
to continue with the pregnancy were therefore not evaluated. No maternal
complications were reported. All women who had a feticide delivered
stillbirths.

Discussion

In South Africa, there are no known national data on LTOP and
feticide for fetal abnormalities, nor are there guidelines and
legislature on feticides. In the literature, establishing clear
guidelines is an issue of debate. (12) Despite the provision of free
maternity services in South Africa, many women book late for antenatal
care. This situation is compounded by lack of resources and skills in
performing obstetric scans, missed early diagnosis, late evolution of
certain abnormalities, delay in referral to tertiary centres and late
decision regarding TOP when a severe congenital abnormality is
diagnosed. It is therefore not surprising that the number of fetal
abnormalities detected after clinical viability is high compared with
affluent countries. Further management of such pregnancies poses a major
decision-making challenge for the pregnant woman and her family, and
also for the physician and other health workers who must manage the
pregnancy.

Several academic units in South Africa perform feticide for severe
fetal abnormalities detected after 22 - 24 weeks' gestation. In
KZN, the Fetal Medicine Unit at IALCH has established guidelines for
LTOP. Contrary to the belief that religion plays a major role in
end-of-life decision for the unborn baby, we found that the
decision-making processes was not influenced by maternal age, parity,
social status or GA at diagnosis of fetal anomaly. This retrospective
audit could not analyse the influence of partners and other family
members on the decision making.

Our highest prevalence of severe fetal abnormalities was in
primigravidas (38.7%) and those between ages of 15 and 24 (43.5%) Older
women are at higher risk for fetal abnormalities, and in one-fifth of
our cases of severe fetal abnormalities the mother was over 35 years
old. The lower prevalence of fetal abnormalities in our patients aged
>35 years may be due to the smaller number of women in this age
category and the nature of the anomalies.

Structural abnormalities were more common than aneuploidy in late
pregnancy. The commonest fetal abnormality involved the CNS, with
hydrocephalus being the commonest brain abnormality. The highest
acceptance rate for LTOP was in women between the ages of 25 and 34
(80.6%) and with 2 or fewer children. Women aged >35 years and those
with more than 3 children had the lowest acceptance rates (66.0% and
55.9%, respectively). Eighty-one per cent of women at GA 24-25 weeks and
71.6% at GA >35 weeks accepted TOP (p>0.05). Although these
figures are not significantly different, it seems that, as human nature
would predict, the more advanced the gestation, the more difficult the
decision-making process becomes. The type of fetal abnormality also
affected acceptance of LTOP by the woman and her family. Although not
statistically significant, the acceptance rate was higher for the more
lethal anomalies such as multiple congenital abnormalities (90.0%) than
for less lethal ones such as spina bifida (59.2%) or anomalies where the
prognosis is less certain such as complex cardiac anomalies (62.5%)
(p=0.086).

Concerning the procedure, our results show a direct correlation
between the dose of KCl and advancing gestation at the time of
performance of feticide. Various methods of feticide with differing
success rates are described, including intra-umbilical lidocaine and
KCl,8-13 intracardiac KCl,9 cardiac tamponade with normal saline10 and
aspiration of blood from the fetal heart.11 One group5 also uses
intra-umbilical sufantenil for fetal analgesia before administering the
lethal drug. As fetal death with intracardiac KCl injection is rapid,
the role of fetal analgesia is uncertain. We concur with the Queen
Charlotte's group that intracardiac injection of KCl is an
effective method of feticide in LTOP for severe congenital
abnormalities. (9)

To our knowledge, no studies have reported prevalence of fetal
abnormalities and the indications for and acceptance rate of LTOP in
low- and middle-income countries. We hope to increase public awareness
of the available treatment options when a severe or complex abnormality
is detected at a late gestation and to provide appropriate counselling
for couples and families. This study also highlights the need for our
health system to enhance professional support for women who request
LTOP.

Limitations

The safety and efficacy of the feticide procedure was based on the
experience and expertise of one fetal medicine specialist (LG), who
performed all the procedures. The number of women with fetal
abnormalities in this study was also not a true reflection of the
incidence of fetal abnormalities/birth defects in the province of KZN,
since not every woman with a fetal anomaly was seen at this unit. The
distant geographical locations in KZN resulted in some women being lost
to follow-up. In addition, the perinatal outcomes of women who declined
termination were not evaluated and autopsies for severe fetal anomalies
were not performed, for reasons beyond the scope of this paper.

Conclusion

Our study shows that the type of fetal anomaly rather than the
demographic details of the patient or the GA at diagnosis affect the
decision to accept or decline LTOP. Our most frequent indication for
LTOP was brain abnormalities, followed by chromosomal abnormalities.
Intracardiac KCl administered under direct vision induces immediate
asystole and appears to be a relatively safe and effective method for
LTOP. However, KCl is associated with potentially serious maternal
side-effects. Further studies are required to determine the minimum
dosage of intracardiac KCl to achieve the desired effect.

(5.) Graham RH, Mason K, Rankin J, Robson, SC. The role of feticide
in the context of late termination of pregnancy: a qualitative study of
health professionals' and parents' views. Prenatal Diagnosis
2009;29(9):875-881. [http://dx.doi.org/10.1002/pd.2297]